This research is to investigate the mechanism for the control of DNA synthesis in normal and malignant cells. Our focus is to determine the role of zinc in DNA polymerization in vitro and the nature of the cellular requirement for zinc in DNA replication. The following studies will be carried out: (1) Establish if animal and viral DNA polymerases including viral "reverse transcriptases" are generically zinc metalloenzymes and define the function of zinc in catalysis by these enzymes. (2) Analyze the effects of different metal chelators on DNA synthesis in vitro and determine if any of these agents can be used to identify and to inhibit, selectively, DNA polymerases from RNA tumor viruses. (3) Determine the mechanism for the inhibition of DNA replication in human lymphocytes by metal chelators. (4) Compare the effects of different chelators on DNA replication in normal and malignant cells. BIBLIOGRAPHIC REFERENCES: On the fidelity of DNA replication II. Characterization of polynucleotides with errors in base-pairing synthesized by avian myeloblastosis deoxyribonucleic acid polymerase. Battula, N., and Loeb, L.A. J. Biol. Chem. 250: 4405-4409. 1975. On mutagenic DNA polymerase and malignancy. Loeb, L.A., Battula, N., and Springgate, C.F. In: Fundamental Aspects of Neoplasia, A. A. Gottlieb-Editor, Springer-Verlag Publishers, New York, N.Y. pp. 243-255. 1975.